The Overlap Index as a means of evaluating early tau-PET signal reliability

Abstract

In tau positron emission tomography (tau-PET), a reliable method to detect early tau accumulation in the brain is crucial. Noise, artifacts, and off-target uptake impede detection of subtle true positive ligand binding. We hypothesize that identifying voxels with stable activity over time can enhance detection of true positive tau. Methods: 339 participants in the clinical spectrum ranging from clinically unimpaired to Alzheimer’s Disease Dementia underwent ≥2 serial tau-PET scans with flortaucipir. The “overlap index” (OI) method was proposed to detect spatially identical, voxel-wise standardized uptake value ratio (SUVR) elevation when seen sequentially in serial tau-PET scans. The association of OI with tau accumulation, clinical diagnosis, and cognitive findings was evaluated. Results: OI showed good dynamic range in the low-SUVR window. Only OI was able to identify subgroups with increasing tau-PET signal in low SUVR meta-ROI groups. OI showed improved association with early clinical disease progression and cognitive scores versus meta-ROI SUVR measures. Conclusion: OI was more sensitive to tau signal elevation and longitudinal change than standard ROI measures, suggesting it is a more sensitive method for detecting early, subtle deposition of neurofibrillary tangles.